Hypothermic machine perfusion of cadaveric kidneys: clinical utility, metabolic mechanisms and methods of optimisation

Hypothermic machine perfusion (HMP) is a dynamic method of preserving kidneys ex vivo with established clinical benefits over static cold storage (SCS). The aim of the first part of this thesis was to determine whether HMP influences clinical outcomes in the United Kingdom via registry analysis of a national dataset. In the second part of this thesis, metabolic changes during HMP are explored using nuclear magnetic resonance (NMR) spectroscopy. Chapter 5 describes differences between HMP and SCS conditions using 1D 1H NMR in a porcine donation after circulatory death (DCD) model. Further experimental chapters use perfusion fluid supplemented with the metabolic tracer universally labelled [U13-C] glucose to describe de novo aerobic and anaerobic metabolism in ex vivo kidneys during HMP. Novel developments in tracer-based NMR methodology are discussed early in the thesis. In Chapter 6, perfusion fluid supplemented with [U13-C] glucose was used to demonstrate several benefits of supplementing perfusion fluid with oxygen during HMP in a porcine DCD model. In the final section, modified [U13-C] glucose perfusion fluid demonstrated differences in de novo metabolism in sub-types of cadaveric kidneys prior to transplantation in a clinical study which also aimed to correlate metabolism with clinical outcome